Comparison of an Initial Risk-Based Testing Strategy vs Usual Testing in Stable Symptomatic Patients With Suspected Coronary Artery Disease
Authors: Pamela S. Douglas, Michael G. Nanna, Michelle D. Kelsey, Eric Yow, Daniel B. Mark, Manesh R. Patel, Campbell Rogers, James E. Udelson, Christopher B. Fordyce, Nick Curzen, Gianluca Pontone, Pál Maurovich-Horvat, Bernard De Bruyne, John P. Greenwood, Victor Marinescu, Jonathon Leipsic, Gregg W. Stone, Ori Ben-Yehuda, Colin Berry, Shea E. Hogan, Bjorn Redfors, Ziad A. Ali, Robert A. Byrne, Christopher M. Kramer, Robert W. Yeh, Beth Martinez, Sarah Mullen, Whitney Huey, Kevin J. Anstrom, Hussein R. Al-Khalidi, Sreekanth Vemulapalli, Anthony N DeMaria, Andrew Kahn, Robert A. Pelberg, Stuart J. Pocock, Binita Shah, Ozgu M. Issever, Marc Bonaca, David J. Engel, W. Schuyler Jones, Derek Chow, Patricia Cowper, Melanie Daniels, Yanhong Li, Weibing Xing, Michael Barry, Stephen Bloom, David Buck, Jane Cao, Jeffrey Carstens, Justin Carter, Benjamin Chow, George Chrysant, Jason Cole, Derek Connolly, Ryan Daly, Sorin Danciu, Melissa Daubert, Roderick Deano, Peter Fail, Timothy Fairbairn, Maros Ferencik, Thomas Hauser, Peter Haworth, Mohammad Hojjati, Angela Hoye, Mark Ibrahim, Fuad Jan, Clemens Kadalie, Dinesh Kalra, Ronald Karlsberg, Steven Kindsvater, John Kobayashi, David Landers, James Lee, Diana Litmanovich, Scott Matson, David McAllister, Gerald McCann, Mark Meier, Nicolai Mejevoi, Bela Merkely, Jamaluddin Moloo, Michael Morris, Darra Murphy, Nasar Nallamothu, Anna Narezkina, Katarina Nelson, Tuan Nguyen, Koen Nieman, Prabhjot Nijjar, Peter O'Kane, Amit Patel, Hena Patel, Thomas Phiambolis, Amit Pursnani, Mark Rabbat, Steven Raible, Frederic Resnic, Michael Salerno, Daniel Sauri, Uwe O.P.J. Schoepf, Moneal Shah, Vincent Sorrell, Michael Turner, Michael Walls, Jonathan Weir-McCall, Frederick Welt, Andrew Zurick
Journal: JAMA Cardiology (2023)

Importance Trials showing equivalent or better outcomes with initial evaluation using coronary computed tomography angiography (cCTA) compared with stress testing in patients with stable chest pain have informed guidelines but raise questions about overtesting and excess catheterization. Objective To test a modified initial cCTA strategy designed to improve clinical efficiency vs usual testing (UT). Design, Setting, and Participants This was a pragmatic randomized clinical trial enrolling participants from December 3, 2018, to May 18, 2021, with a median of 11.8 months of follow-up. Patients from 65 North American and European sites with stable symptoms of suspected coronary artery disease (CAD) and no prior testing were randomly assigned 1:1 to precision strategy (PS) or UT. Interventions PS incorporated the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) minimal risk score to quantitatively select minimal-risk participants for deferred testing, assigning all others to cCTA with selective CT-derived fractional flow reserve (FFR-CT). UT included site-selected stress testing or catheterization. Site clinicians determined subsequent care. Main Outcomes and Measures Outcomes were clinical efficiency (invasive catheterization without obstructive CAD) and safety (death or nonfatal myocardial infarction [MI]) combined into a composite primary end point. Secondary end points included safety components of the primary outcome and medication use. Results A total of 2103 participants (mean [SD] age, 58.4 [11.5] years; 1056 male [50.2%]) were included in the study, and 422 [20.1%] were classified as minimal risk. The primary end point occurred in 44 of 1057 participants (4.2%) in the PS group and in 118 of 1046 participants (11.3%) in the UT group (hazard ratio [HR], 0.35; 95% CI, 0.25-0.50). Clinical efficiency was higher with PS, with lower rates of catheterization without obstructive disease (27 [2.6%]) vs UT participants (107 [10.2%]; HR, 0.24; 95% CI, 0.16-0.36). The safety composite of death/MI was similar (HR, 1.52; 95% CI, 0.73-3.15). Death occurred in 5 individuals (0.5%) in the PS group vs 7 (0.7%) in the UT group (HR, 0.71; 95% CI, 0.23-2.23), and nonfatal MI occurred in 13 individuals (1.2%) in the PS group vs 5 (0.5%) in the UT group (HR, 2.65; 95% CI, 0.96-7.36). Use of lipid-lowering (450 of 900 [50.0%] vs 365 of 873 [41.8%]) and antiplatelet (321 of 900 [35.7%] vs 237 of 873 [27.1%]) medications at 1 year was higher in the PS group compared with the UT group (both P &amp;amp;lt; .001). Conclusions and Relevance An initial diagnostic approach to stable chest pain starting with quantitative risk stratification and deferred testing for minimal-risk patients and cCTA with selective FFR-CT in all others increased clinical efficiency relative to UT at 1 year. Additional randomized clinical trials are needed to verify these findings, including safety. Trial Registration ClinicalTrials.gov Identifier: NCT03702244